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PubMed1998

Association between characteristics of locomotion and accomplishment of life habits in children with cerebral palsy.

BACKGROUND AND PURPOSE: "Handicap situation" is defined in the literature as "a disruption in the accomplishment of a person's life habits (activities of daily living and social roles)." The purpose of this study was to determine the strength of association between various types of locomotion and the accomplishment of life habits, which is an indicator of the occurrence of handicap situations in children with cerebral palsy. SUBJECTS: Ninety-eight children with cerebral palsy, aged 5 to 17.8 years (mean = 10.5, SD = 3.5), were recruited. METHODS: The Life Habits Assessment was used to evaluate handicap situations in activities of daily living and social roles. Types of locomotion, the Pediatric Functional Independence Measure (locomotion section), and 2 tests representing functional activities (walking speed and stair climbing) were used as characteristics of locomotion. RESULTS: Locomotion capabilities were associated with the accomplishment of activities of daily living and social roles. Performance in variables related to locomotion, number of associated problems, and type of cerebral palsy explained 17% to 74% of the total variance in accomplishment of life habits in children who walked without technical aids. CONCLUSION AND DISCUSSION: The results suggest that locomotion might influence the accomplishment of life habits. Other factors, however--such as environmental barriers--should also be examined to determine their impact on the occurrence of handicap situations.

Activities of Daily Living↗

PubMed1999

Depression of muscle and cutaneous afferent-evoked monosynaptic field potentials during fictive locomotion in the cat.

1. Monosynaptic extracellular field potentials evoked by electrical stimulation of ipsilateral hindlimb nerves carrying muscle group I, II and cutaneous afferents were examined during fictive locomotion. Fifty-eight field potentials were recorded in the dorsal and intermediate laminae throughout the mid-lumbar to first sacral segments and fictive locomotion was evoked by mesencephalic locomotor region (MLR) stimulation in paralysed decerebrate cats. 2. The majority (96 %) of group I, II and cutaneous-evoked field potentials were decreased during fictive locomotion. Group I, cutaneous and dorsal group II potentials were reduced on average to about 80 % of control values. Group II field potentials recorded in the intermediate laminae were reduced to a mean of 49 % of control values. Cyclic variations in field potential amplitude between the flexion and extension phases were observed in 24 of 45 cases analysed. Of those 24 field potentials, the two group I and four cutaneous field potentials were smaller during the flexion phase. All eleven group II and the remaining seven cutaneous fields were smaller during extension. In all but two cases, these cyclic variations were smaller than the tonic depression upon which they were superimposed. 3. In 7/9 group II field potentials examined, reductions (on average to 85 % of control) began with the onset of MLR stimulation that produced tonic activity in the motor nerves before the onset of rhythmic alternating, locomotor discharges. In six of the seven cases the field potential depression increased with the establishment of fictive locomotion. This observation and the cyclic modulation of field potentials during fictive locomotion suggests that the depression was strongly linked to the operation of the spinal locomotor circuitry. 4. Depression of the monosynaptic components of the field potentials suggests a reduction in synaptic transmission from primary afferents to first-order spinal interneurones during fictive locomotion. Accordingly, the larger depression of intermediate group II field potentials may indicate a preferential reduction in transmission from group II afferents to interneurones located in intermediate spinal laminae. 5. Flexion reflexes evoked by group II and cutaneous afferents were also depressed during MLR-evoked fictive locomotion. The possibility that this depression results from a reduction in transmission from primary afferents, and in particular from group II afferents, ending on interneurones in the intermediate laminae is discussed.

Animals↗

PubMed2000

Group I disynaptic excitation of cat hindlimb flexor and bifunctional motoneurones during fictive locomotion.

The incidence of short latency excitation of motoneurones innervating flexor and bifunctional muscles evoked by group I intensity (<= 2 x threshold) electrical stimulation of hindlimb muscle nerves was investigated during fictive locomotion in decerebrate cats. Intracellular recordings were made from hindlimb motoneurones in which action potentials were blocked by intracellular diffusion of a lidocaine (lignocaine) derivative (QX-314) and fictive locomotion was evoked by electrical stimulation of the midbrain. Few motoneurones (16%) received group I-evoked oligosynaptic excitation in the absence of fictive locomotion. During fictive locomotion 39/44 (89%) motoneurones innervating ankle, knee or hip flexor muscles and 18/28 (64%) motoneurones innervating bifunctional muscles received group I-evoked oligosynaptic EPSPs. In flexor motoneurones, locomotor-dependent excitation was present in both step cycle phases but largest during flexion. In bifunctional motoneurones, EPSPs were often largest at the transition between flexion and extension phases. Activation of homonymous afferents most consistently evoked the largest locomotor-dependent excitation (amplitude up to 4.6 mV), but in some cases stimulation of heteronymous flexor or bifunctional muscle nerves evoked large EPSPs. EPSP amplitude became maximal as stimulation intensity was increased to about twice threshold. This suggests that tendon organ afferents can evoke group I EPSPs during locomotion. The EPSPs resulting from brief, small stretches of extensor digitorum longus tendons indicate that group Ia muscle spindle afferents can also evoke the group I excitation of flexors. Stimulation of extensor group I afferents did not result in excitation of flexor motoneurones. The mean latency of locomotor-dependent group I excitation in flexor and bifunctional motoneurones was 1.64 +/- 0.16 ms, indicating a path consisting of a single interneurone interposed between group I afferents and motoneurones innervating flexor and bifunctional muscles. This disynaptic excitation is analogous to that recorded in extensor motoneurones and evoked from extensor group I afferents during locomotion. Differences in the phase dependence and sources of group I excitation to flexor and extensor motoneurones during locomotion suggest the existence of separate groups of excitatory interneurones exciting flexor and extensor motoneurones. The wide distribution of group I disynaptic excitation in motoneurones innervating extensor, flexor and bifunctional muscles acting on hip, knee and ankle joints suggests that these pathways can play an important role in the reinforcement of ongoing locomotor activity throughout the limb.

Afferent Pathways↗

PubMed1997

Cardiovascular responses during spontaneous overground locomotion in freely moving decerebrate cats.

To examine whether the cerebrum is essential for producing the rapid cardiovascular adjustment at the beginning of overground locomotion, we examined heart rate (HR), mean arterial blood pressure (MAP), and integrated electromyogram (iEMG) of the forelimb triceps brachialis muscle in freely moving decerebrate cats during locomotion. Two to four days after decerebration surgery performed at the level of the precollicular-premammillary body, the animals spontaneously produced coordinated overground locomotion, supporting body weight. HR began to increase immediately before the onset of iEMG, and MAP began to rise almost simultaneously with the iEMG onset. Their increases in HR and MAP (24 +/- 3 beats/min and 22 +/- 4 mmHg) were sustained during locomotion. Sinoaortic denervation (SAD) did not affect the abrupt changes in HR and MAP at the beginning of locomotion (0-4 s from the onset of iEMG), whereas SAD had a contrasting effect during the subsequent period, a decrease in the HR response (9 +/- 1 beats/min) and an increase in the MAP response (30 +/- 3 mmHg). These results suggest that the cerebrum and the rostral part of the diencephalon are not essential for producing the rapid cardiovascular adjustment at the beginning of spontaneous overground locomotion. The arterial baroreflex does not contribute to this rapid adjustment but plays an important role in regulating the cardiovascular responses during the later period of spontaneous locomotion.

Animals↗

PubMed2005

Localization of spinal neurons activated during locomotion using the c-fos immunohistochemical method.

The c-fos immunohistochemical method of activity-dependent labeling was used to localize locomotor-activated neurons in the adult cat spinal cord. In decerebrate cats, treadmill locomotion was evoked by electrical stimulation of the mesencephalic locomotor region (MLR). Spontaneous or MLR-evoked fictive locomotion was produced in decerebrate animals paralyzed with a neuromuscular blocking agent. After bouts of locomotion during a 7- to 9-h time period, the animals were perfused and the L3-S1 spinal cord segments removed for immunohistochemistry. Control animals were subjected to the same surgical procedures but no locomotor task. Labeled cells were concentrated in Rexed's laminae III and IV of the dorsal horn and laminae VII, VIII, and X of the intermediate zone/ventral horn after treadmill locomotion. Cells in laminae VII, VIII, and X were labeled after fictive locomotion, but labeling in the dorsal horn was much reduced. In control animals, c-fos labeling was a small fraction of that observed in the locomotor animals. The results suggest that labeled cells in laminae VII, VIII, and X are premotor interneurons involved in the production of locomotion, whereas the laminae III and IV cells are those activated during locomotion due to afferent feedback from the moving limb. c-fos-labeled cells were most numerous in the L5-L7 segments, consistent with the distribution of locomotor activated neurons detected through the use of MLR-evoked field potentials.

Animals↗

PubMed2003

Effects of intrathecal glutamatergic drugs on locomotion. II. NMDA and AP-5 in intact and late spinal cats.

In a previous article, we have shown that, in cats, intrathecal injections of N-methyl-D-aspartate (NMDA) in the first few days after spinalization at T13 do not induce locomotion as in many other spinal preparations. This is in contrast to alpha-2 noradrenergic receptor stimulation, which can trigger locomotion at this early stage. However, it is known that spinal cats do recover spontaneous locomotion in the absence of descending noradrenergic pathways and that the spinal pattern generator must then depend on other neurotransmitters still present in the cord such as excitatory amino acids. In the present paper, therefore we look at the effects of intrathecal NMDA, a glutamatergic agonist, and 2-amino-5-phosphonovaleric acid (AP-5), an NMDA receptor blocker, in both intact and late spinal cats. Low doses of NMDA had no major effect on the locomotor pattern in both intact and late spinal cats. Larger doses of NMDA in the chronic spinal cat initially produced an increase in the general excitability followed by more regular locomotion. AP-5 in intact cats caused a decrease in the amplitude of the flexion reflex and induced a bilateral foot drag as well as some decrease in weight support but it did not prevent locomotion. However, in late spinal cats, the same dose of AP-5 blocked locomotion completely. These results indicate that NMDA receptors may be critical for the spontaneous expression of spinal locomotion. It is proposed that the basic locomotor rhythmicity in cats is NMDA-dependent and that normally this glutamatergic mechanism is modulated by other neurotransmitters, such as 5-HT and NA.

2-Amino-5-phosphonovalerate↗

PubMed2007

Characteristics and mechanisms of locomotion induced by intraspinal microstimulation and dorsal root stimulation in spinal cats.

Intraspinal microstimulation (ISMS) through a single microelectrode can induce locomotion in cats spinalized at T(13) 1 wk before (untrained) or after 3-5 wk of treadmill training. Here we study the optimal parameters of ISMS and the characteristics of locomotion evoked. ISMS was applied in the dorsal region of segments L(3)-S(1) at different lateralities (midline to 2.5 mm) and after an intravenous injection of clonidine (noradrenergic agonist). Kinematics and electromyographic recordings were used to characterize locomotion. ISMS could induce a bilateral locomotor pattern similar to that obtained with perineal stimulation, and the characteristics of locomotion varied according to the spinal segment stimulated. Mechanisms by which ISMS could evoke locomotion were then investigated by stimulating, inactivating, or lesioning different spinal structures. Dorsal root stimulation (DRS), just like ISMS, could evoke a variety of ipsi- and bilateral nonlocomotor movements as well as locomotor responses. This suggests that sensory afferent pathways are involved in the production of locomotion by ISMS. Microinjections of yohimbine (noradrenergic antagonist) in L(3) and L(4) segments or a complete second spinal lesion at L(3)-L(4) abolished all locomotor activity evoked by ISMS applied at more caudal segments. Progressive dorsoventral spinal lesions at L(3) or L(4) and restricted ventral lesions at L(4) further suggest that the integrity of the ventral or ventrolateral funiculi as well as the L(3)-L(4) segments are critical for the induction of locomotion by ISMS at L(5) to S(1) or by DRS at these caudal segments.

Adrenergic alpha-Antagonists↗

PubMed2005

Mid-lumbar segments are needed for the expression of locomotion in chronic spinal cats.

In acute experiments performed in decerebrated and spinalized (T13) cats, an intraspinal injection of clonidine, a noradrenergic agonist, restricted to mid-lumbar segments L3-L4, can induce hindlimb locomotion, whereas yohimbine, a noradrenergic antagonist, can block spinal locomotion, and a second spinal lesion at L4 can abolish all locomotor activity. In the present study, we investigated whether the abolition of locomotion after this second spinal lesion was due to an acute spinal shock or to the functional disconnection of the rostral and caudal lumbar segments. In seven cats, first spinalized at T13 and having recovered treadmill locomotion, a second transection was performed at lower lumbar levels. Video and electromyographic recordings were used to evaluate locomotor performance. Results show that after a second transection at L2 or rostral L3 levels, spinal locomotion was maintained; when the second lesion was performed at caudal L3 or L4, all locomotor activity was abolished even after several weeks of attempted locomotor training; vigorous fast paw shakes (FPS) were observed in all cases; and after an intraperitoneal injection of clonidine in cats with a second transection below L4, perineal stimulation induced hyperextension of the hindlimbs but no locomotion. Considering that the main motoneuron pools of the hindlimbs are caudal to L4 and are still functional after the second spinal transection, as evidenced by the presence of FPS, we conclude that the mid-lumbar spinal segments are essential for the specific expression of spinal locomotion but not necessarily for other rhythmic motor patterns.

Adrenergic alpha-Agonists↗

PubMed1987

Ia inhibitory interneurons and Renshaw cells as contributors to the spinal mechanisms of fictive locomotion.

The activity of selected single alpha-motoneurons, Renshaw cells (RCs), and Ia inhibitory interneurons (IaINs) during fictive locomotion was recorded via microelectrodes in decerebrate (precollicular-postmammillary) cats in which fictive locomotion was induced by stimulation of the mesencephalic locomotor region. The interrelationships in the timing and frequency of discharge among these three interconnected cell types were determined by comparing their averaged step cycle firing histograms, which were normalized in reference to motoneuron activity recorded in ventral root filaments. Previous findings that RCs are rhythmically active during locomotion and discharge in phase with the motoneurons from which they are excited were confirmed, and further details of the phase relationships between RC and alpha-motoneuron activity during fictive locomotion were obtained. Flexor and extensor RCs became active after the onset of flexor and extensor motoneuron activity, respectively. Maximal activity in extensor RCs occurred at the end of the extension phase coincidental with the onset of hyperpolarization and a decrease in activity in extensor motoneurons. Maximal flexor RC activity occurred during middle to late flexion and was temporally related to the onset of reduced flexor motoneuron activity. The IaINs recorded in the present experiments were rhythmically active during fictive locomotion, as previously reported. The quadriceps IaINs were mainly active during the extension phase of the step cycle, along with extensor RCs. Thus the known inhibition of quadriceps IaINs by RCs coupled to quadriceps and other extensor motoneurons is obviously not sufficient to interfere with the appropriate phasing of IaIN activity and reciprocal inhibition during fictive locomotion, as had been speculated. Most of the quadriceps IaINs analyzed exhibited a decrease in discharge frequency at the end of the extension phase of the step cycle, which was coincidental with increased rates of firing in extensor RCs. These data are consistent with the possibility that extensor RCs contribute to the reduction in quadriceps IaIN discharge at the end of the extension phase of the step cycle. The possibility that IaIN rhythmicity during fictive locomotion arises from periodic inhibition, possibly from Renshaw cells, was tested by stimulating the reciprocal inhibitory pathway throughout the fictive step cycle. The amplitude of Ia inhibitory postsynaptic potentials (IPSPs) varied significantly throughout the fictive step cycle in 14 of the 17 motoneurons tested, and, in 11 of these 14 motoneurons, the Ia IPSPs were maximal during the phase of the step cycle in which the motoneuron was most

Animals↗

PubMed1998

Modulation of oligosynaptic cutaneous and muscle afferent reflex pathways during fictive locomotion and scratching in the cat.

We have compared state-dependent transmission through oligosynaptic (minimally disynaptic) reflex pathways from low-threshold cutaneous and muscle afferents to some flexor and extensor lumbosacral motoneurons during fictive locomotion and scratching in decerebrate unanesthetized cats. As reported in earlier work, oligosynaptic cutaneous excitatory postsynaptic potentials (EPSPs) in flexor digitorum longus (FDL) and inhibitory postsynaptic potentials (IPSPs) in extensor digitorum (EDL) longus motoneurons were enhanced markedly during the early flexion phase of fictive locomotion. We show in this paper that, in contrast, these cutaneous reflex pathways were depressed markedly during all phases of fictive scratching. On the other hand, disynaptic EPSPs produced by homonymous and synergist group I muscle afferents in flexor (tibialis anterior and EDL) motoneurons were present and strongly modulated during both fictive locomotion and scratching. During both actions, these disynaptic group I EPSPs appeared or exhibited the largest amplitude when the motoneuron membrane potential was most depolarized and the parent motor pool was active. There was an interesting exception to the simple pattern of coincident group I EPSP enhancement and motoneuron depolarization. During locomotion, disynaptic group I EPSPs in both FDL and flexor hallucis longus (FHL) motoneurons cells were facilitated during the extension phase, although FDL motoneurons were relatively hyperpolarized whereas FHL cells were depolarized. The reverse situation was found during fictive scratching; group I EPSPs were facilitated in both FDL and FHL cells during the flexion phase when FDL motoneurons were depolarized and FHL cells were relatively hyperpolarized. These observations suggest that the disynaptic EPSPs in these two motor nuclei are produced by common interneurons. Reciprocal disynaptic inhibitory pathways from group Ia muscle afferents to antagonist motoneurons were also active and subject to phase-dependent modulation during both fictive locomotion and scratching. In all but one cell tested, reciprocal disynaptic group Ia IPSPs were largest during those phases in which the motoneuron membrane potential was relatively hyperpolarized and the parent motor pool was inactive. Oligosynaptic PSPs in motoneurons produced by stimulation of the mesencephalic locomotor region (MLR) were modulated strongly during fictive locomotion but were suppressed powerfully throughout fictive scratching. Large cord dorsum potentials generated by MLR stimuli also were suppressed markedly during fictive scratching. These results allow certain inferences about the organization of interneurons in the pathways examined. They also suggest that the central pattern generators that produce fictive locomotion and scratching are organized differently.

Afferent Pathways↗

PubMed1998

Effects of intrathecal alpha1- and alpha2-noradrenergic agonists and norepinephrine on locomotion in chronic spinal cats.

Noradrenergic drugs, acting on alpha adrenoceptors, have been found to play an important role in the initiation and modulation of locomotor pattern in adult cats after spinal cord transection. There are at least two subtypes of alpha adrenoceptors, alpha1 and alpha2 adrenoceptors. The aim of this study was to investigate the effects of selective alpha1 and alpha2 agonists in the initiation and modulation of locomotion in adult chronic cats in the early and late stages after complete transection at T13. Five cats, chronically implanted with an intrathecal cannula and electromyographic (EMG) electrodes were used in this study. Noradrenergic drugs including alpha2 agonists (clonidine, tizanidine, and oxymetazoline) and an antagonist, yohimbine, one alpha1 agonist (methoxamine), and a blocker, prazosin, as well as norepinephrine were injected intrathecally. EMG activity synchronized to video images of the hindlimbs were recorded before and after each drug injection. The results show differential effects of alpha1 and alpha2 agonists in the initiation of locomotion in early spinal cats (i.e., in the first week or so when there is no spontaneous locomotion) and in the modulation of locomotion and cutaneous reflexes in the late-spinal cats (i.e., when cats have recovered spontaneous locomotion). In early spinal cats, all three alpha2 agonists were found to initiate locomotion, although their action had a different time course. The alpha1 agonist methoxamine induced bouts of nice locomotor activity in three spinal cats some hours after injection but only induced sustained locomotion in one cat in which the effects were blocked by the alpha1 antagonist prazosin. In late spinal cats, although alpha2 agonists markedly increased the cycle duration and flexor muscle burst duration and decreased the weight support or extensor activity (effects blocked by an alpha2 antagonist, yohimbine), alpha1 agonist increased the weight support and primarily the extensor activity of the hindlimbs without markedly changing the timing of the step cycle. Although alpha2 agonists, especially clonidine, markedly reduced the cutaneous excitability and augmented the foot drag, the alpha1 agonist was found to increase the cutaneous reflex excitability. This is in line with previously reported differential effects of activation of the two receptors on motoneuron excitability and reflex transmission. Noradrenaline, the neurotransmitter itself, increased the cycle duration and at the same time retained the cutaneous excitability, thus exerting both alpha1 and alpha2 effects. This work therefore suggests that different subclasses of noradrenergic drugs could be used to more specifically target aspects of locomotor deficits in patients after spinal injury or diseases.

Adrenergic alpha-1 Receptor Agonists↗

PubMed1999

Stimulation of a restricted region in the midline cerebellar white matter evokes coordinated quadrupedal locomotion in the decerebrate cat.

In the reflexively standing acute decerebrate cat, we have previously shown that pulse train microstimulation of the hook bundle of Russel in the midline of the cerebellar white matter, through which crossed fastigiofugal fibers decussate, augments the postural tone of neck, trunk, fore-, and hindlimb extensor muscles. In the present study we examined the possible role of such stimulation in evoking locomotion as the animal is supported by a rubber hammock with its feet contacting the moving surface of a treadmill. We were able to provoke well-coordinated, bilaterally symmetrical, fore- and hindlimb movements, whose cycle time and pattern were controlled by appropriate changes in stimulus intensity and treadmill speed. We carefully and systematically mapped this cerebellar locomotor region (CLR) through repeated dorsoventral penetrations with a glass-coated tungsten microelectrode in a single animal and between animals. We found that the optimal locus for evoking locomotion was centered on the midline, at Horsley-Clarke coordinates H0 and P7.0, and extended over a rostrocaudal and dorsolateral range of approximately 0.5 mm. The lowest effective stimulus intensity at the optimal site was in the range of 5-8 microA. Along penetration tracks to left or right of the midline, effective stimulus intensity increased and evoked locomotor patterns were no longer symmetrical, but rather shifted toward the contralateral limbs. In the same animals, controlled locomotion was evoked by stimulating the mesencephalic locomotor region (MLR). With concomitant stimulation of the optimal sites in the CLR and the MLR, each at subthreshold strength, locomotor movements identical to those seen with suprathreshold stimulation of each site alone were evoked. With concomitant stimulation at suprathreshold strength for each site, locomotion became vigorous, with a shortened cycle time. After making ablative lesions at either the CLR or MLR (unilateral or bilateral), controlled locomotion was still evoked at the prior stimulus strength by stimulating the remaining site. Together, these results demonstrate that selective stimulation of the hook bundle of Russel in the midsagittal plane of the cerebellar white matter evokes "controlled" locomotion identical to that evoked by stimulating the MLR. We have shown that the fastigial nucleus is one of the supraspinal locomotion inducing sites and that it can independently and simultaneously trigger brain stem and spinal locomotor subprograms formerly believed to be the domain of various brain stem regions including the MLR and the subthalamic locomotor region.

Animals↗

PubMed1993

Effect of surgery on peripheral blood lymphocyte locomotion through type I collagen.

BACKGROUND: Locomotion of peripheral blood lymphocytes (PBL) through peritumoral matrix is obligatory for tumor cell killing. The authors investigated the effect of surgery on lymphocyte locomotion and compared it with the effect on natural killer cell cytotoxicity (NKCC). METHODS: PBL from 12 patients with cancer were assessed for locomotion in Type I rat-tail collagen. Preoperative and postoperative locomotion (after 20 hours of incubation) and NKCC were estimated. RESULTS: Locomotion of lymphocytes through collagen increased significantly after operation in 6 of 12 patients, whereas only 1 of 12 had a decrease (P < 0.001). Short-term (20-hour incubation) exposure of the locomotory HSB cell line to patient plasma samples did not affect their migration. NKCC, as estimated against K562 target cells with the use of the 51Cr-release assay, decreased 5-50% after operation in 9 of 12 patients (P = 0.006). No correlation could be demonstrated between the changes in locomotion and NKCC (regression analyses), nor were identifiable clinical factors associated with these changes. CONCLUSIONS: Locomotion of PBL through collagen increases after operation in patients with cancer, whereas possibly independent factors may decrease postoperative NKCC.

Cell Movement↗

PubMed2002

Localised depletion of polymerised actin at the front of Walker carcinosarcoma cells increases the speed of locomotion.

Spontaneously migrating Walker carcinosarcoma cells usually form lamellipodia at the front. Combined treatment with 10(-5)M colchicine and 10(-7)M latrunculin A produces large defects in the cortical F-actin layer at the leading front and suppresses lamellipodia. However, the cortical actin layer at the rear is intact and shows myosin IIA accumulation. These cells, showing no or little detectable cortical F-actin at the front and no morphologically recognisable protrusions, migrate faster than control cells with lamellipodia and an intact cortical actin layer. This documents that the cortical actin layer or actin-powered force generation at the front is redundant for locomotion. Colchicine and latrunculin A have synergistic effects in compromising the cortical layer at the front and in increasing the speed of locomotion, but antagonistic effects on the relative amount of F-actin per cell. Colchicine but not latrunculin A, can increase the proportion of polarised and locomoting cells under appropriate conditions. Locomotion and polarity of cells treated with latrunculin A and colchicine is inhibited at latrunculin A concentrations >10(-7)M, by the myosin inhibitor BDM or the ROCK inhibitor Y-27632. Colchicine and Y-27632 have antagonistic effects on polarity and the speed of locomoting cells. The data show that locomotion of metazoan cells, which normally form lamellipodia, can be driven by actomyosin contraction behind the front (cell body, uropod). They are best compatible with a cortical contraction/frontal expansion model, but they are not compatible with models implying that actin polymerisation or actomyosin contraction at the front drive locomotion of the cells studied.

Actinin↗

PubMed1988

Polymorphonuclear leukocyte locomotion is insensitive to lowered cytoplasmic calcium levels.

Chemotactic factors stimulate the rate of locomotion of polymorphonuclear leukocytes (PMNs). To investigate the importance of cytoplasmic calcium we have examined the ability of the chemotactic peptide N-formylnorleucyl eucylphenalanine (FNLLP) to stimulate the locomotion of PMNs whose cytoplasmic calcium levels were reduced by incubation in EGTA or in EGTA plus the calcium ionophores, ionomycin or A23187. Locomotion was assayed by migration through micropore filters and by time-lapse videomicroscopy. Cells in EGTA exhibited similar or slightly reduced rates of locomotion compared to cells in Hanks' balanced salt solution (HBSS). The peptide dose dependence for the stimulation of locomotion was similar in medium containing calcium or EGTA. The presence of 1 microM ionophore plus EGTA had no effect on the stimulation of locomotion by peptide. The presence of ionophores (1 microM) plus external calcium inhibited locomotion.

Animals↗

PubMed1995

Impairment of lymphocyte locomotion in the tumor microenvironment and the effect of systemic immunotherapy with liposome-encapsulated muramyl-tripeptide-phosphatidylethanolamine.

The ability of the lymphocytes to move through the interstitium is obligatory to the immune response. We previously showed that tumor-infiltrating lymphocytes (TIL) from human melanoma and renal cell carcinoma demonstrate a dramatic decrease in their spontaneous locomotion through three-dimensional collagen gel when compared with peripheral blood lymphocytes (PBL) and lymph node lymphocytes. To determine if this decrease is caused by contact with tumor cells, or mediated through certain diffusible factors, we examined the effects of autologous tumor cells on the locomotion of PBL in a model system where tumor cells were separated from lymphocytes by a 3-mm layer of gelled collagen. After 21-22 h incubation in chamber slides, locomotion distances were assessed in the presence and absence of tumor and normal cells. In the presence of tumor cells, PBL from 14 of 18 patients displayed substantial (466.5 +/- 2.7 microns compared to control 568.9 +/- 10.9 microns, P < 0.001) loss of motility. Inhibition was more prominent in melanoma patients than in renal cell carcinoma patients. Thus the impaired locomotion previously observed in TIL was at least partially due to the presence of tumor. The locomotion of TIL was restored in four of five melanoma patients treated with liposome-encapsulated muramyl-tripeptide-phosphatidylethanolamine (L-MTP-PE). Furthermore, in six of seven examined L-MTP-PE-treated patients, an increase in intrinsic PBL locomotion during the first month of the therapy was observed. These results suggest that the environment of the tumor is not conducive to locomotion of advancing lymphocytes and the therapeutic intervention may ameliorate the loss of lymphocytic infiltration.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1997

Changes in gravity inhibit lymphocyte locomotion through type I collagen.

Immunity relies on the circulation of lymphocytes through many different tissues including blood vessels, lymphatic channels, and lymphoid organs. The ability of lymphocytes to traverse the interstitium in both nonlymphoid and lymphoid tissues can be determined in vitro by assaying their capacity to locomote through Type I collagen. In an attempt to characterize potential causes of microgravity-induced immunosuppression, we investigated the effects of simulated microgravity on human lymphocyte function in vitro using a specialized rotating-wall vessel culture system developed at the Johnson Space Center. This very low shear culture system randomizes gravitational vectors and provides an in vitro approximation of microgravity. In the randomized gravity of the rotating-wall vessel culture system, peripheral blood lymphocytes did not locomote through Type I collagen, whereas static cultures supported normal movement. Although cells remained viable during the entire culture period, peripheral blood lymphocytes transferred to unit gravity (static culture) after 6 h in the rotating-wall vessel culture system were slow to recover and locomote into collagen matrix. After 72 h in the rotating-wall vessel culture system and an additional 72 h in static culture, peripheral blood lymphocytes did not recover their ability to locomote. Loss of locomotory activity in rotating-wall vessel cultures appears to be related to changes in the activation state of the lymphocytes and the expression of adhesion molecules. Culture in the rotating-wall vessel system blunted the ability of peripheral blood lymphocytes to respond to polyclonal activation with phytohemagglutinin. Locomotory response remained intact when peripheral blood lymphocytes were activated by anti-CD3 antibody and interleukin-2 prior to introduction into the rotating-wall vessel culture system. Thus, in addition to the systemic stress factors that may affect immunity, isolated lymphocytes respond to gravitational changes by ceasing locomotion through model interstitium. These in vitro investigations suggest that microgravity induces non-stress-related changes in cell function that may be critical to immunity. Preliminary analysis of locomotion in true microgravity revealed a substantial inhibition of cellular movement in Type I collagen. Thus, the rotating-wall vessel culture system provides a model for analyzing the microgravity-induced inhibition of lymphocyte locomotion and the investigation of the mechanisms related to lymphocyte movement.

Animals↗

PubMed1988

Hypothalamic substrates for brain stimulation-induced patterns of locomotion and escape jumps in the rat.

The hypothalamic response area for electrically induced locomotion was determined using moveable electrodes and discriminant analysis as an appropriate statistical technique. At 241 out of 641 stimulated sites locomotion was induced. The distribution of locomotion sites is relatively diffuse. Discriminant analysis of both positive and negative electrode localizations yields areas with high, intermediate or low probability of inducing the response. The response is considered to be mediated by fibres of the subpallido-pedunculopontine system, which includes the mesencephalic locomotor region. Different categories of exploratory and flight-directed locomotion were distinguished, and response areas for both categories were determined. In addition the response area for escape jumps was delimited. Exploratory locomotion is mainly induced from the lateral hypothalamus, while flight-directed locomotion and escape jumps are evoked from the medial hypothalamus. The response area for exploratory locomotion reflects the lateral hypothalamic distribution of the subpallidal projection to the mesencephalic locomotor region. A diffuse substrate for flight behavior seems to occupy almost the entire medial hypothalamus. It is concluded that a locomotor subroutine subserving different behavioural mechanisms can be activated at many hypothalamic sites.

Animals↗